Fat and Bone: An Odd Couple

In this review, we will first discuss the concept of bone strength and introduce how fat at different locations, including the bone marrow, directly or indirectly regulates bone turnover. We will then review the current literature supporting the mechanistic relationship between marrow fat and bone and our understanding of the relationship between body fat, body weight and bone with emphasis on its hormonal regulation. Finally, we will briefly discuss the importance and challenges of accurately measuring the fat compartments using non-invasive methods. This review highlights the complex relationship between fat and bone and how these new concepts will impact on our diagnostic and therapeutic approaches in the very near future

Developments in the Imaging of Brown Adipose Tissue and its Associations with Muscle, Puberty, and Health in Children

Fusion positron emission and computed tomography (PET/CT) remains the gold-standard imaging modality to non-invasively study metabolically active brown adipose tissue (BAT). It has been widely applied to studies in adult cohorts. In contrast, the number of BAT studies in children has been few. This is largely limited by the elevated risk of ionizing radiation and radionuclide tracer usage by PET/CT and the ethical restriction of performing such exams on healthy children. However, metabolically active BAT has a significantly higher prevalence in pediatric patients, according to recent literature. Young cohorts thus represent an ideal population to examine the potential relationships of BAT to muscle development, puberty, disease state, and the accumulation of white adipose tissue. In turn, magnetic resonance imaging (MRI) represents the most promising modality to overcome the limitations of PET/CT. The development of rapid, repeatable MRI techniques to identify and quantify both metabolically active and inactive BAT non-invasively and without the use of exogenous contrast agents or the need for sedation in pediatric patients are critically needed to advance our knowledge of this tissue’s physiology

Brown adipose tissue in the buccal fat pad during infancy.

BackgroundThe buccal fat pad (BFP) is an encapsulated mass of adipose tissue thought to enhance the sucking capabilities of the masticatory muscles during infancy. To date, no conclusive evidence has been provided as to the composition of the BFP in early postnatal life.ObjectiveThe purpose of this study was to examine whether the BFP of neonates and infants is primarily composed of white adipose tissue (WAT) or brown adipose tissue (BAT).Materials and methodsThe percentage of fat in the BFP in 32 full-term infants (16 boys and 16 girls), aged one day to 10.6 months, was measured using magnetic resonance imaging (MRI) determinations of fat fraction.ResultsBFP fat fraction increased with age (r = 0.67; P<.0001) and neonates had significantly lower values when compared to older infants; 72.6 ± 9.6 vs. 91.8 ± 2.4, P<.0001. Multiple regression analysis indicated that the age-dependent relationship persisted after accounting for gender, gestational age, and weight percentile (P = .001). Two subjects (aged one and six days) depicted a change in the MRI characteristics of the BFP from primarily BAT to WAT at follow-up examinations two to six weeks later, respectively. Histological post-mortem studies of a 3 day and 1.1 month old revealed predominantly BAT and WAT in the BFP, respectively.ConclusionThe BFP is primarily composed of BAT during the first weeks of life, but of WAT thereafter. Studies are needed to investigate the contributions of BAT in the BFP to infant feeding and how it is altered by postnatal nutrition

Contribution of the Vertebral Posterior Elements in Anterior–Posterior DXA Spine Scans in Young Subjects

Because DXA is a projection technique, anterior–posterior (AP) measurements of the spine include the posterior elements and the vertebral body. This may be a disadvantage because the posterior elements likely contribute little to vertebral fracture resistance. This study used QCT to quantify the impact of the posterior elements in DXA AP spine measures. We examined 574 subjects (294 females and 280 males), age 6–25 yr, with DXA and QCT. QCT measures were calculated for the cancellous bone region and for the vertebral body including and excluding the posterior elements. DXA data were analyzed for the entire L3 vertebra and for a 10-mm slice corresponding to the QCT scan region. BMC and BMD were determined and compared using Pearson's correlation. The posterior elements accounted for 51.4 ± 4.2% of the total BMC, with a significant difference between males (49.9 ± 4.0%) and females (52.8 ± 3.9%, p < 0.001). This percentage increased with age in younger subjects of both sexes (p < 0.001) but was relatively consistent after age 17 for males and 16 for females (p > 0.10). DXA areal BMD and QCT volumetric BMD correlated strongly for the whole vertebra including the posterior elements (R = 0.83), with BMC measures showing a stronger relationship (R = 0.93). Relationships were weaker when excluding the posterior elements. We conclude that DXA BMC provides a measure of bone that is most consistent with QCT and that the contribution of the posterior elements is consistent in young subjects after sexual maturity

Comparative analysis of microRNA expression in mouse and human brown adipose tissue

BACKGROUND: In small mammals brown adipose tissue (BAT) plays a predominant role in regulating energy expenditure (EE) via adaptive thermogenesis. New-born babies require BAT to control their body temperature, however its relevance in adults has been questioned. Active BAT has recently been observed in adult humans, albeit in much lower relative quantities than small mammals. Comparing and contrasting the molecular mechanisms controlling BAT growth and development in mice and humans will increase our understanding or how human BAT is developed and may identify potential therapeutic targets to increase EE. MicroRNAs are molecular mechanisms involved in mouse BAT development however, little is known about the miRNA profile in human BAT. The aims of this study were to establish a mouse BAT-enriched miRNA profile and compare this with miRNAs measured in human BAT. To achieve this we firstly established a mouse BAT enriched-miRNA profile by comparing miRNAs expressed in mouse BAT, white adipose tissue and skeletal muscle. Following this the BAT-enriched miRNAs predicted to target genes potentially involved in growth and development were identified. METHODS: MiRNA levels were measured using PCR-based miRNA arrays. Results were analysed using ExpressionSuite software with the global mean expression value of all expressed miRNAs in a givensample used as the normalisation factor. Bio-informatic analyses was used to predict gene targets followed by Ingenuity Pathway Analysis. RESULTS: We identified 35 mouse BAT-enriched miRNAs that were predicted to target genes potentially involved in growth and development. We also identified 145 miRNAs expressed in both mouse and human BAT, of which 25 were enriched in mouse BAT. Of these 25 miRNAs, miR-20a was predicted to target MYF5 and PPAR&gamma;, two important genes involved in brown adipogenesis, as well as BMP2 and BMPR2, genes involved in white adipogenesis. For the first time, 69 miRNAs were identified in human BAT but absent in mouse BAT, and 181 miRNAs were expressed in mouse but not in human BAT. CONCLUSION: The present study has identified a small sub-set of miRNAs common to both mouse and human BAT. From this sub-set bioinformatics analysis suggested a potential role of miR-20a in the control of cell fate and this warrants further investigation. The large number of miRNAs found only in mouse BAT or only in human BAT highlights the differing molecular profile between species that is likely to influence the functional role of BAT across species. Nevertheless the BAT-enriched miRNA profiles established in the present study suggest targets to investigate in the control BAT development and EE

BMD loci contribute to ethnic and developmental differences in skeletal fragility across populations: Assessment of evolutionary selection pressures

Bone mineral density (BMD) is a highly heritable trait used both for the diagnosis of osteoporosis in adults and to assess bone health in children. Ethnic differences in BMD have been documented, with markedly higher levels in individuals of African descent, which partially explain disparity in osteoporosis risk across populations. To date, 63 independent genetic variants have been associated with BMD in adults of Northern-European ancestry. Here, we demonstrate that at least 61 of these variants are predictive of BMD early in life by studying their compound effect within two multiethnic pediatric cohorts. Furthermore, we show that within these cohorts and across populations worldwide the frequency of those alleles associated with increased BMD is systematically elevated in individuals of Sub-Saharan African ancestry. The amount of differentiation in the BMD genetic scores among Sub-Saharan and non-Sub-Saharan populations together with neutrality tests, suggest that these allelic differences are compatible with the hypothesis of selective pressures acting on the genetic determinants of BMD. These findings constitute an explorative contribution to the role of selection on ethnic BMD differences and likely a new example of polygenic adaptation acting on a human trait

Evaluation of Cortical Bone by Computed Tomography

The purpose of this study was to determine the minimum thickness of cortical bone required for the accurate measurement of cortical material density by computed tomography (CT) and to establish normal reference values. A phantom with several wall thicknesses of bone-like material was constructed to simulate various cortical widths. The CT density at each level of thickness was measured on a GE 9800 CT scanner and on the OsteoQuant, a special CT scanner optimized for the measurement of bone in the extremities. The minimum width required to attain the correct material density was determined for each scanner. Additionally, the material density and width of the cortex in the radius and/or femur were measured by CT in 761 healthy subjects, ages 4-84 years. The minimum thickness necessary for an accurate density evaluation of the walls of the phantom by CT was 2-2.5 mm; below these thresholds the values fell in a linear way relative to width. In humans, the material density of cortical bone in the appendicular skeleton was not influenced by height or weight, and the values were similar for all subjects, as long as the cortical width was above 2-2.5 mm. The cortical width increased with age up to 30 years and decreased from 50 years on. We conclude that the material density of cortical bone in the appendicular skeleton can be measured accurately by CT if the thickness of the cortex exceeds 2-2.5 mm

Evaluation of Cortical Bone by Computed Tomography

The purpose of this study was to determine the minimum thickness of cortical bone required for the accurate measurement of cortical material density by computed tomography (CT) and to establish normal reference values. A phantom with several wall thicknesses of bone-like material was constructed to simulate various cortical widths. The CT density at each level of thickness was measured on a GE 9800 CT scanner and on the OsteoQuant, a special CT scanner optimized for the measurement of bone in the extremities. The minimum width required to attain the correct material density was determined for each scanner. Additionally, the material density and width of the cortex in the radius and/or femur were measured by CT in 761 healthy subjects, ages 4-84 years. The minimum thickness necessary for an accurate density evaluation of the walls of the phantom by CT was 2-2.5 mm; below these thresholds the values fell in a linear way relative to width. In humans, the material density of cortical bone in the appendicular skeleton was not influenced by height or weight, and the values were similar for all subjects, as long as the cortical width was above 2-2.5 mm. The cortical width increased with age up to 30 years and decreased from 50 years on. We conclude that the material density of cortical bone in the appendicular skeleton can be measured accurately by CT if the thickness of the cortex exceeds 2-2.5 mm

Gilsanz V. Differential effect of marrow adiposity and visceral and subcutaneous fat on cardiovascular risk in young, healthy adults

Background—Adipose tissue is an endocrine organ that influences many metabolic processes and accumulates in different depots, including the bone marrow. While the negative associations between visceral fat (VF) or subcutaneous fat (SF) and cardiovascular disease (CVD) risks are well known, the relation between marrow fat (MF) and metabolic risk is unexplored. Objectives—We examined the relations between these three fat depots and whether CVD risks are associated to marrow adiposity. Design—observational cross sectional study Subjects and Methods—Computed tomography was used to measure VF, SF and MF depots in 131 healthy young adults (60 females, 71 males; 16-25 years of age). Weight, body mass index (BMI), waist and hip circumferences, blood pressure (BP), carotid intima media thickness (CIMT) and serum levels of lipids, glucose and insulin were also measured. Results—Regardless of gender, MF was not associated to values of VF or SF, anthropometric measures, or lipid or carbohydrate serum levels (P&gt;0.05 for all). In contrast, VF was associated to SF (r’s = 0.74 for females, 0.78 for males; both P’s &lt;0.0001) and these depots were related to anthropometric parameters (r’s between.69 and.87; all P’s &lt;0.0001) and to most measures of lipids, glucose or insulin (r’s between.25 and.62). Conclusions—Marrow adiposity in young men and women is independent of visceral and subcutaneous fat, and is not associated to CVD risk. These findings do not support the concept that marrow adiposity is involved in the comorbidities related to fat accumulation in other compartments. Keywords marrow fat; visceral fat; subcutaneous fat; cardiovascular risk; computed tomograph